The MA Center for Birth Defects Research and Prevention (MCBDRP) proposes to: continue participation in the National Birth Defects Prevention Study and pilot new methods; perform environmental and genetic etiologic research studies in our areas of particular expertise; utilize the unique MA Pregnancy to Early Life Longitudinal database to conduct follow-up research on children with birth defects; and pilot test methods to translate research findings into prevention messages. The MA Center will continue its leadership role on medication use in pregnancy and related risks. As NBDPS pilot projects, the MCBDRP will: validate CATI responses on use of assisted reproductive technology; test novel ways to assess variation in time and space clustering of gastroschisis; assess whether a medication identification booklet improves the reliability of maternal medication responses; and analyze first trimester serum screening results to examine hypotheses related to birth defects etiology. In year one, MCBDRP will complete 5 etiologic research projects that cover medically significant and/or common risk factors: 1) Relation of non-steroidal anti-inflammatory drugs to the risk of birth defects (NSAIDs are frequently used by pregnant women, so even a small increased risk for birth defects could be important because of the number of potentially affected offspring); 2) Vasoactive medications and vascular disruption defects (Findings will be important because these medications are popular and vascular disruption pathogenesis is poorly understood); 3) Drugs for nausea and vomiting of pregnancy and risk of congenital heart defects (If drugs used as a remedy for such a common condition cause birth defects, an opportunity for sizable prevention exists); 4) Glycemic load and non-neural tube defects (Dietary patterns have changed over the past decades, with many persons replacing consumption of proteins and fats with carbohydrates; it is therefore critical to identify the possible impact of such high-glycemic diets on risks of birth defects); and 5) De novo copy number variants and nonsyndromic conotruncal heart defects (Studies of this type of genetic abnormality represents a powerful new tool in studies of risk factors for birth defects that will further understanding of mechanisms of embryologic development that lead to this and other birth defects). Additional projects that will continue beyond year 1 include a study of birth defect risks associated with medications that contain the endocrine-disruptor phthalates. This project will also serve as a model for assessing risk associated with inactive ingredients in medications. Epidemiologic studies of other relevant medication and environmental exposures will be conducted, as will clinical descriptive studies of heart, limb, and diaphragm defects, of which MA has particular clinical expertise. MCBDRP will also expand genetic work to: 1) identify de novo copy number variants associated with other birth defects; and 2) identify pharmacogenetic determinants of birth defects. Finally, the MCBDRP will utilize and evaluate, where possible, multiple communication pathways to raise awareness of NBDPS findings and their implications.